Dataset Information

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

ABSTRACT: Purpose:The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema. Methods:Patients (n = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics. Results:After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups. Conclusions:BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema. Translational Relevance:Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.

SUBMITTER: Lang GE

PROVIDER: S-EPMC7396196 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

Lang Gabriele E GE Tadayoni Ramin R Tang Wenbo W Barth Claudia C Weiss-Haljiti Cornelia C Chong Victor V

Translational vision science & technology 20200330 4

<h4>Purpose</h4>The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild vis ...[more]

PMID: 32818112

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Project description:PURPOSE:To investigate the relationship between diabetic macular edema (DME) and the choroidal layer thickness in diabetic patients. METHODS:This is a retrospective observation study. Three hundred eighteen eyes of 159 diabetes mellitus (DM) patients and age-matched 100 eyes of 79 healthy controls were enrolled. DME was defined as over 300 ?m in the central retinal subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector. The central choroidal thickness (CCT), as well as inner and outer layers were determined based on enhanced depth imaging (EDI)-OCT. Diabetic patients with/without systemic diabetic treatments (DT) at the start of this study was defined as DT+ and DT-, respectively. The number of eyes examined was 62 and 256 eyes in DME+and DME-groups, respectively. DM patients were further subdivided into 4 groups with/without DME and DT; DME+DT+(35 eyes), DME-DT+(159 eyes), DME+DT-(27 eyes), and DME-DT-group (97 eyes). Multiple comparisons on CCT layers including control and each DM group were statistically examined. RESULTS:The total CCT layer was 254±83, 283±88, and 251±70 ?m in the control, DME+, and DME-group, respectively. A total CCT layer in DME+was significantly thicker than the DME-group (P < 0.05). The outer CCT layer was 195±75, 222±83, and 193±63 ?m in the control, DME+, and DME-group, respectively. The outer CCT layer in DME+ was significantly thicker than the DME-group (P < 0.05). In the subdivided groups, the total CCT layers in the control, DME+DT+, DME-DT+, DME+DT-and DME-DT-groups were 254±83, 274±88, 247±66, 290±84 and 258±75 ?m, respectively. The outer CCT layers in each group were 195±75, 214±83, 189±58, 228±77, and 201±70 ?m, respectively. Total CCT and the outer layer in DME+DT-was significantly thicker than the DME-DT+group (each P < 0.05). In contrast, there was no significant difference in inner layer between the groups. CONCLUSIONS:The total and outer CCT layers of diabetic eyes were significantly thickened in the DME+DT-as compared with the DME-DT+group, suggesting that CCT may be related to the pathology of DME.

Project description:BackgroundThe comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear.ObjectivesThis meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting.MethodsA systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence.ResultsFive RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = -4.75 ETDRS letters, 95% CI = [-7.73, -1.78], p = 0.002) and reduction in retinal thickness (WMD = -93.02 μm, 95% CI = [-153.23, -32.82], p = 0.002) at months 4-6 compared to low-dose (1-2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes.ConclusionsThe RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4-6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

Dataset Information

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

Publications

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

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